The goal of Project 0006 will be to examine in detail the biological basis of "treatment failure". The first series of experiments will examine a possible microbial component of treatment failure and include the hypotheses that: 1) the etiologic species are resistant to the adjunctive antibiotic employed; 2) the antimicrobial agent does not reach periodontal sites in levels sufficient to suppress the pathogens, 3) the pathogens are of a distinct, highly virulent clonal type; 4) the etiologic organisms colonize sites which are inaccessible to mechanical and/or antimicrobial treatment. A second set of experiments will examine the host component of treatment failure and include the hypotheses that: 1) the host's "response system" (PMNs, antibody, complement) cannot kill the subject's subgingival species; 2) the host mounts an inadequate immunological response manifested by an over or under production of antibody, or production of ineffective antibody; 3) the host responds to subgingival species with an "overly exuberant" (damaging) inflammatory response. Subjects in Project 0005 identified as treatment failures (test) will enter Project 0006 (minimum n=30). A matched, "treatment success" subject (control) will be identified for each test subject, who is of the same race, sex, age, and medical status group. Clinical, demographic, microbiological and immunological characteristics of both test and control subjects will be available from data collected in Project 0005. All test and control subjects will be evaluated at the baseline visit of Project 0006 for the following additional parameters: 1) the presence of species resistant to tetracycline, 2) clonal type of P. gingivalis and C. rectus, 3) level of enteric organisms and yeasts, and the presence of unusual species (by PCR), 4) ability to deliver systemically-administered tetracycline to periodontal sites, 5) ability of host defense system to kill the subject's subgingival pathogens, 6) antibody response to subgingival species and 7) levels of local inflammatory mediators. If these data suggest an "appropriate therapy", that therapy will be instituted. When an "appropriate therapy" is not apparent, 1 of 2 intensive antimicrobial therapies will be instituted. If during the course of treatment, a tooth must be extracted for periodontal reasons, microorganisms in penetrating the dentinal tubules of the root will be sought and identified. Three, 6 and 12 months after completion of therapy, all subjects will be monitored using clinical and laboratory assessments.